Water → HCID 58529888, compound

HRID 1972820Notes

Reaction equation

HRID 1972820 reaction equation
Br[C:2]1[C:3]([CH3:19])=[C:4]([CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2.[CH2:20]([N:27]1[CH:35]=[C:34]2[C:29]([CH:30]=[C:31](B3OC(C)(C)C(C)(C)O3)[CH:32]=[CH:33]2)=[N:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:20]([N:27]1[CH:35]=[C:34]2[C:29]([CH:30]=[C:31]([C:2]3[C:3]([CH3:19])=[C:4]([CH2:12][N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)[N:5]4[C:10]=3[C:9]([NH2:11])=[N:8][CH:7]=[N:6]4)[CH:32]=[CH:33]2)=[N:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 579552405-Bromo-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-Indazole

Product 1

HCID 58529888HCID 58529888, compoundYield 7.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-bromo-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (150 mg, 0.46 mmol) and tetrakis(triphenylphosphine)palladium(0) (159 mg, 0.14 mmol), in degassed DMF (3.0 mL) was added 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (184 mg, 0.55 mmol), K2CO3 (153 mg, 1.10 mmol), and H2O (0.5 mL). The mixture was degassed and heated (100° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous Na2CO3 solution (25 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was purified by preparative HPLC using a gradient elution from 10% to 70% acetonitrile to obtain 15 mg (7%) of the desired product. 1H-NMR (DMSO-d6) 8.56 (s, 1H), 7.85 (s, 1H), 7.80 (d, 1H), 7.54 (s, 1H), 7.32-7.38 (m, 5H), 7.02 (d, 1H), 5.65 (s, 2H), 3.81 (s, 2H), 2.53-2.50 (m, 4H), 2.43-2.40 (m, 4H), 2.10 (s, 3H); LC-MS [M+H]+=454, RT=2.30 min.

Workup

  1. customThe mixture was degassed
  2. temperaturecooled to rt
  3. customThe mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous Na2CO3 solution (25 mL)
  4. customThe layers were separated
  5. washthe organic phase was washed
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by preparative HPLC
  9. washa gradient elution from 10% to 70% acetonitrile

Sources & evidence

ORD record
ord-a91d556aefbc466babaa413b477e72ab
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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